title: STAT5b deficiency: lessons from STAT5b gene mutations.
abstract: Growth hormone (GH) regulates insulin-like growth factor (IGF)-I production primarily through activation of the GH receptor (GHR)-signal transducer and activator of transcription (STAT)-5b signaling cascade. One of four STAT proteins (STAT1, -3, -5a and -5b) activated by the GH-GHR system, the critical importance of STAT5b in IGF-I production became evident with the identification of homozygous, autosomal recessive STAT5b mutations in patients who presented with severe postnatal growth failure, growth hormone insensitivity syndrome (GHIS) and marked IGF-I deficiency. Unlike GHIS due to GHR mutations, patients carrying STAT5b mutations also presented with chronic pulmonary disease and evidence of perturbations of T-cell homeostasis. At present, no single treatment(s) is available to improve both poor statural growth and immune deficiency. Continued clinical evaluations of patients with STAT5b mutations and elucidating the impact of the mutation on STAT5b structure and function, are important to understanding the pathophysiology of this rare, complex, disease (MIM 245590).
authors.affiliation: Department of Pediatrics, Oregon Health Sciences University, Portland, OR 97239, USA. hwav@ohsu.edu
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
authors.forename: Kari
authors.initials: K
authors.lastname: Nadeau
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
mesh_terms: D000818:Animals; D005260:Female; D006130:Growth Disorders / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology; D053614:Janus Kinase 2 / Q000502:physiology; D046150:Laron Syndrome / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D009154:Mutation; D050799:STAT5 Transcription Factor / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D025521:Tumor Suppressor Proteins; D007334:Insulin-Like Growth Factor I; C507924:JAK2 protein, human; D053614:Janus Kinase 2